We are continuing to investigate the subcellular localization and effect of overexpressing neuregulin in hippocampal neurons. Our previous studies suggest that neuregulin exists in clusters in hippocampal neurons. We are examining whether these neuregulin clusters associate with specific subcellular regions, and whether the pattern of distribution is regulated during neuronal development. In addition, we are building expression constructs to express different isoforms of neuregulins, and will compare the difference between their subcellular localization and effect on hippocampal neuron development. Consistent with the genetic association of neuregulin with schizophrenia, our work in progress, have found that neuregulin overexpression altered the morphogenesis of synapses. This observation indicates that neuregulin might be involved in abnormal synaptic transmission in psychiatric disorders, which presumably is an important cellular mechanism for the pathophysiology of schizophrenia.